Effects of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III open tibia fractures treated with unreamed nails—A clinical and health-economic analysis

Abstract

Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is licensed in Europe for open tibia fractures treated with unreamed nails. However, there is limited data available on the specific use of rhBMP-2 in combination with unreamed nails for open tibia fractures. The intention of the current study was to evaluate the medical and health-economic effects of rhBMP-2 in Gustilo-Anderson grade III open tibia fractures treated with unreamed nails based on individual patient data from two previously published studies. Linear regression analysis was performed on raw data of 90 patients that were either treated by standard of care with soft tissue management and unreamed nailing (SOC group) (n=50) or with rhBMP-2 in addition to soft tissue management and unreamed nailing (rhBMP-2 group) (n=40). For all types of revision, a significant lower percentage of patients (27.5%) of the rhBMP-2 group had to be revised compared to 48% of the patients of the SOC group (p=0.04). When only invasive secondary interventions such as bone grafting and nail exchange were considered, there was also a statistically significant reduction in the rhBMP-2 group with a revision rate of 10.0% (4 of 40 patients) compared to the SOC group with a revision rate of 28.0% (14 of 50 patients) (p=0.01). Mean fracture healing time of 228 days in the rhBMP-2 compared to 266 days in the SOC group was not statistically significant (p=0.24). Health-economic analysis based on a societal perspective with calculation of overall treatment costs after initial surgery and including productivity losses revealed savings of €6,239 per patient for Germany and €4,752 for the UK in favour of rhBMP-2 which was mainly driven by reduction of productivity losses. In conclusion, rhBMP-2 reduces secondary interventions in patients with grade III open tibia fractures treated with an unreamed nail and its use leads to financial savings for Germany and the UK from a societal perspective.

The Biological Basis for Nonunions

“…Recombinant human BMP-2 is currently available and approved for clinical use in the United States and Europe for adult patients with acute open tibial fractures that are treated with intramedullary nailing 30,37 . Recombinant BMP-7 is currently available with marketing authorization for clinical use in Europe for the treatment of tibial nonunions of at least nine months' duration.…”

Bone morphogenetic protein‐2 is a stronger inducer of osteogenesis within muscle tissue than heterodimeric bone morphogenetic protein‐2/6 and ‐2/7: Implications for expedited gene‐enhanced bone repair

“…Bone morphogenetic proteins (BMPs) are some of the most prominent and most widely studied osteogenic molecules with a strong effect on the osteogenic differentiation and proliferation of stem cells. Human recombinant BMP‐2 received approval from the Food and Drug Administration in 2002 for clinical applications and has been frequently used for the treatment of complicated fractures, non‐unions and spinal fusion procedures, as well as to regenerate maxillofacial bone . Despite its widespread clinical use, it became obvious that delivery of BMP‐2 needs optimization as a result of its short biological half‐life .…”

Inhibin α‐subunit inhibits BMP9‐induced osteogenic differentiation through blocking BMP/Smad signal and activating NF‐κB signal in mesenchymal stem cells

“…But, the explicit about the effect of inhibins on bone development remains unclear still. Bone morphogenetic proteins (BMPs) have been widely acknowledged to stimulate bone growth and a few BMP members have already been used clinically . Both BMPs and inhibins are the members of TGF‐β superfamily, but the effect of inhibins on BMPs remains unclear.…”